Abstract:
:The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and claudin-4 (Cld3,4) were 'preferentially' expressed in Aire(+) mTECs. In early ontogeny, Cld3,4(hi) TECs derived from the most apical layer of the stratified thymic anlage first expressed known mTEC markers such as UEA-1 ligand and MTS10. We provide evidence that such Cld3,4(hi) UEA-1(+) TECs represented the initial progenitors specified for Aire(+) mTECs, whose development crucially required NF-kappaB-inducing kinase and the adaptor molecule TRAF6. Our results suggest that Aire(+) mTECs represent terminally differentiated cells in a unique lineage arising during thymic organogenesis.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Hamazaki Y,Fujita H,Kobayashi T,Choi Y,Scott HS,Matsumoto M,Minato Ndoi
10.1038/ni1438subject
Has Abstractpub_date
2007-03-01 00:00:00pages
304-11issue
3eissn
1529-2908issn
1529-2916pii
ni1438journal_volume
8pub_type
杂志文章abstract::Naturally arising CD25(+)CD4(+) regulatory T cells actively maintain immunological self-tolerance. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. A reduction in their number or function can also elicit tumor immunity, whereas their antigen-specific population expansion can establish ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1178
更新日期:2005-04-01 00:00:00
abstract::Regulatory T cells (T(reg) cells) develop from progenitor thymocytes after the engagement of T cell antigen receptors (TCRs) with high-affinity ligands, but the underlying molecular mechanisms are still unclear. Here we show that the Nr4a nuclear receptors, which are encoded by immediate-early genes upregulated by TCR...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2520
更新日期:2013-03-01 00:00:00
abstract::In T lymphocytes, the mitogen-activated protein kinase (MAPK) p38 regulates pleiotropic functions and is activated by canonical MAPK signaling or the alternative activation pathway downstream of the T cell antigen receptor (TCR). Here we found that senescent human T cells lacked the canonical and alternative pathways ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2981
更新日期:2014-10-01 00:00:00
abstract::The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), tha...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0698-1
更新日期:2020-07-01 00:00:00
abstract::Inflammation is a fundamental protective response that sometimes goes awry and becomes a major cofactor in the pathogenesis of many chronic human diseases, including cancer. Here we review the evolutionary relationship and opposing functions of the transcription factor NF-κB in inflammation and cancer. Although it see...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2060
更新日期:2011-07-19 00:00:00
abstract::The ligation of Toll-like receptors (TLRs) leads to rapid activation of dendritic cells (DCs). However, the metabolic requirements that support this process remain poorly defined. We found that DC glycolytic flux increased within minutes of exposure to TLR agonists and that this served an essential role in supporting ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2833
更新日期:2014-04-01 00:00:00
abstract::Despite accumulating evidence that regulatory T cells play a crucial role in preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR)...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/86302
更新日期:2001-04-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature immunology
pub_type: 已发布勘误
doi:10.1038/s41590-020-0739-9
更新日期:2020-08-01 00:00:00
abstract::T cell exhaustion has a major role in failure to control chronic infection. High expression of inhibitory receptors, including PD-1, and the inability to sustain functional T cell responses contribute to exhaustion. However, the transcriptional control of these processes remains unclear. Here we demonstrate that the t...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2046
更新日期:2011-05-29 00:00:00
abstract::Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of costimulatory molecules to function across species barriers. We describe a strategy to inhibit costimulation that exploits species differences using the model of porcine pancreatic islet transplantation into mice. Mice were immunized with ch...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/77853
更新日期:2000-08-01 00:00:00
abstract::Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/87766
更新日期:2001-05-01 00:00:00
abstract::Ingested antigens lead to the generation of effector T cells that secrete interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of influencing naive T cells in their immediate environment to do the same. Using chimeric mice generated by aggregation of two genotypically different embryos, we fou...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1077
更新日期:2004-06-01 00:00:00
abstract::The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly unders...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0582-z
更新日期:2020-02-01 00:00:00
abstract::Weak T cell antigen receptor (TCR) signals from contact with self ligands act in synergy with antiapoptotic signals induced by interleukin 7 (IL-7) to promote the survival of naive T cells in a resting state. The amount of background TCR signaling in naive T cells is set by post-thymic TCR tuning and operates at an in...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2018
更新日期:2011-06-01 00:00:00
abstract::High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0544-5
更新日期:2019-12-01 00:00:00
abstract::An important function of receptors that signal through immunoreceptor tyrosine-based activation motifs (ITAMs) is to regulate signaling by heterologous receptors. This review describes mechanisms by which ITAM-associated receptors modulate signaling by Toll-like receptors (TLRs), tumor necrosis factor receptor family ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.1706
更新日期:2009-04-01 00:00:00
abstract::During the productive interaction of T cells with antigen-presenting cells (APCs), engaged receptors, including the T cell antigen receptors and their associated tyrosine kinases, assemble into spatially segregated supramolecular activation clusters (SMACs) at the area of cell contact. Here, we studied intracellular s...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni836
更新日期:2002-10-01 00:00:00
abstract::Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threa...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-00826-9
更新日期:2021-01-01 00:00:00
abstract::Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through the mouse T cell receptor-alpha (Tcra) locus suppressed V(alph...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1379
更新日期:2006-10-01 00:00:00
abstract::Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C. Chemokines have roles in immunity and inflammation that affect cell trafficking and activation of T cells as well as cells of the innate immune system. We report here CX3C chemokin...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/90675
更新日期:2001-08-01 00:00:00
abstract::The origin and specification of human dendritic cells (DCs) have not been investigated at the clonal level. Through the use of clonal assays, combined with statistical computation, to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34+ progenitor cells, we found ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3789
更新日期:2017-08-01 00:00:00
abstract::We used high-resolution mass spectrometry to map the cytotoxic T lymphocyte (CTL) proteome and the effect of the metabolic checkpoint kinase mTORC1 on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes, and mTORC1 selectively repressed and promoted expression of a subset of CTL proteins (~10%)....
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3314
更新日期:2016-01-01 00:00:00
abstract::The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechani...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2820
更新日期:2014-03-01 00:00:00
abstract::Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3229
更新日期:2015-09-01 00:00:00
abstract::Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1239
更新日期:2005-09-01 00:00:00
abstract::The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH17 cells) and follicular helper T cells (TFH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells show...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2834
更新日期:2014-04-01 00:00:00
abstract:: ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0309-6
更新日期:2019-02-01 00:00:00
abstract::The survival of T lymphocytes requires sustained, Ca(2+) influx-dependent gene expression. The molecular mechanism that governs sustained Ca(2+) influx in naive T lymphocytes is unknown. Here we report an essential role for the beta3 regulatory subunit of voltage-gated calcium (Ca(v)) channels in the maintenance of na...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1793
更新日期:2009-12-01 00:00:00
abstract::Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in I...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2187
更新日期:2011-11-20 00:00:00
abstract::We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/79738
更新日期:2000-10-01 00:00:00